Recent work in our laboratory and others has suggested that the hyperglycemia of noninsulin dependent diabetic subjects is maintained by increased hepatic glucose production. We have hypothesized that hepatic glucose production is increased due to an appropriate response to the liver to increased fluxes of free fatty acids, and gluconeogenic substrates. The subjects are also characterized by reduced insulin action and reduced peripheral insulin concentrations. In vitro evidence collected in isolated adipocytes has also suggested that there is reduced maximal insulin stimulated glucose transport rates in these individuals, along with increased basal lipolytic rates. In order to define which of these abnormalities might be most responsible for the hyperglycemia of the diabetics we plan a weight loss study to correlate changes in fasting glycemia with changes in these other aspects of carbohydrate metabolism in vivo and in vitro. Noninsulin dependent diabetic subjects with fasting glycemias greater than 200 mg/dl and BMIs greater than 30 will be admitted to the clinical research ward. After 10 days of weight maintenance and adaptation to the research ward diet, studies of body composition, insulin secretion, insulin action, hepatic glucose production and glucose recycling through the Cori cycle, and measurements of abdominal adipocyte metabolism will be made. Subjects will then eat a weight losing diet, calculated as 30% of their weight maintenance requirements, for up to 5 1/2 weeks. This will be followed by another weight maintenance diet of approximately 10 days when the above studies will be repeated. Our hypothesis is that reduction in glycemia associated with reduction in body weight will be best correlated with decreases in hepatic glucose production and glucose recycling through the Cori cycle.